J. Toms

Disease Activity Composite Indices in Patients with Rheumatoid Arthritis and Concomitant Fibromyalgia

We read with great interest the article by Coury, et al 1 comparing patients with rheumatoid arthritis (RA) and concomitant fibromyalgia (RAF). The ambiguous results of this study showed that patients with RAF had significantly higher disease activity measured by the 28-joint Disease Activity Score (DAS-28)2, but significantly more severe joint destruction was revealed in patients with RA. We examined 120 of our patients (29 men, 91 women) with RA according to the American College of Rheumatology (ACR) criteria3 on the presence of concurrent fibromyalgia (FM). All … Address correspondence to Dr. Toms, E-mail: toms.jan{at}seznam.cz

Whipple's Disease: Our Own Experience and Review of the Literature

Whipples disease is a chronic infectious systemic disease caused by the bacterium Tropheryma whipplei. Nondeforming arthritis is frequently an initial complaint. Gastrointestinal and general symptoms include marked diarrhoea (with serious malabsorption), abdominal pain, prominent weight loss, and low-grade fever. Possible neurologic symptoms (up to 20%) might be associated with worse prognosis. Diagnosis is based on the clinical picture and small intestinal histology revealing foamy macrophages containing periodic-acid-Schiff- (PAS-) positive material. Long-term (up to one year) antibiotic therapy provides a favourable outcome in the vast majority of cases. This paper provides review of the literature and an analysis of our 5 patients recorded within a 20-year period at a tertiary gastroenterology centre. Patients were treated using i.v. penicillin G or amoxicillin-clavulanic acid + i.v. gentamicin for two weeks, followed by p.o. doxycycline (100 mg per day) plus p.o. salazopyrine (3 g per day) for 1 year. Full remission was achieved in all our patients.

Risk Factors of Acute Pancreatitis in Oral Double Balloon Enteroscopy

Double balloon enteroscopy (DBE) was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%). Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase). Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

PS5:93 Marginal-zone-like b cells deficiency repeatedly detected in peripheral blood as a possible biomarker of hyposplenism/asplenia in sle

Objective SLE is a disease associated with a risk of serious infections, in case of hyposplenism/asplenia especially by encapsulated bacteria. For opsonization and phagocytosis of these agents are essential IgM natural Abs, produced only by B cells of the splenic marginal zone. Significant deficiency of marginal-zone-like B cell CD19 +CD27+IgM+ subpopulation absolute values x10–6/L in peripheral blood (PB) was demonstrated in a prospective, comparative, cross-over SLE study1; goal of the present study is follow up persistence of this phenomenon. Design and method Sixty adult SLE (ACR/1982, update 1997) pts and 10 age-and sex-matched healthy controls (HC) were enrolled in month O’, and 56 SLE pts also repeatedly after twelve-month-period, i. e. month 12’; overlap syndromes, infection, monoclonal gammopathy and renal failure in SLE under study were excluded. The DuraClone IM panel (Beckman Coulter) was used to identify CD19 +CD27+IgM+B cell subpopulation in PB samples by flow cytometry Navios (Beckman Coulter) with software analysis using Kaluza version 1.2: data obtained were expressed in relative% of PB lymphocytes and absolute values x10–6/L. Parallel analysis of serological SLE biomarkers included C3, C4, ANA/IF (maximal titre), ANA/ELISA, anti-dsDNA/IFCL (maximal titre), andi-dsDNA/ELISA and antinucleosome Abs. Data obtained were statistically processed using Medcalc-Statistical Software programme. Results Significant differences (p<0.001) were obtained between absolute values of CD19 +CD27+IgM+B cells in HC (median 31.36, 95% CI: 24.49 to 63.35) and SLE month O’ (median 9.82, 95% CI: 6.01 to 14.26), and also SLE month 12’ (median 10.09 95% CI: 7.12 to 14.42), but not between values obtained in SLE month O’ and month 12’ (p>0.05); not significant differences were found in analysis using relative% of PB lymphocytes (p>0.05). In SLE month O’ was found a slight significant correlation between absolute values of CD19 +CD27+IgM+B cells and anti-dsDNA/ELISA Abs (rs=−0.28, p=0.034) without a confirmation in month 12’ control (rs=−0.09, p=0.491). Conclusions The data obtained demonstrated persistent character of marginal-zone-like B cells deficiency in peripheral blood, and are suggesting as possible biomarker of functional hyposplenism/asplenia in SLE. Reference . Hrncir Z, et al. Clin Exper Rheumatol2016;34(S99):S-63. Acknowledgement Supported by the research project PROGRES Q40–15.

Methotrexate impact on radiographic progression in biologic-treated rheumatoid arthritis under clinical remission: A case report on monozygotic Caucasian twins:

We describe Caucasian monozygotic twin brothers with rheumatoid arthritis (RA) and discuss influence of predictors to methotrexate (MTX) outcome treatment. Single nucleotide polymorphisms (SNPs) of the MTX metabolic pathways were genotyped. Twins have multiple mutations: a CC mutation of SNP 1298A>C in methylenetetrahydrofolate reductase (MTHFR) gene, CC mutations of three SNPs in the adenosine receptor gene ADORA2A (rs3761422_4217241T>C, rs2267076_4221164T>C, rs2236624_4226593T>C), and a heterozygous genotype in SNPs ATIC_rs2372536_347C>G, MTHFD1_rs2236225_1958G>A. These mutations are known to predict a worse outcome of MTX treatment. The twins had different lifestyles (alcohol drinking and smoking in Twin 1, regular coffee consumption in Twin 2), but a very similar clinical presentation of the outset of RA, radiographic scoring according to the Sharp/van der Heijde method with an almost identical antibodies presentation. The period of the patients before anti-TNFα treatment was characterized by unsuccessful per oral MTX pharmacotherapy in both cases (a low effect of MTX in Twin 1; an early discontinuation of MTX due to an adverse event in Twin 2). In both twins, the outcome of well-controlled anti-TNFα treatment (co-medication with MTX in Twin 1) for 10 years was expressed as low disease activity measured using composite index DAS28. It is interesting that Twin 2 had an unfavorable radiographic scoring after a 10-year follow-up than Twin 1 in spite of the comparable DAS28 in Twin 2 and smoking in Twin 1. In conclusion, co-medication of MTX with biologics may impact on RA radiographic progression despite predicted bad MTX outcome based on pharmacogenetic analysis.

AB0565 Diffuse Alveolar Hemorrhage, Diagnosis, Treatment and 3-Year Prognosis in A Group of 32 Cases of Tertiary Centre

Objectives Diffuse alveolar hemorrhage (DAH) is severe, life-threatening syndrome, affecting the patients with systemic vasculitis and other systemic connective tissue diseases. It can be often the first manifestation of systemic disease. Frequently DAH is the acute incident, which often leads to the rapidly emerging respiratory and/or renal failure with requirement of ventilatory support and with high mortality rate. Methods Diffuse alveolar hemorrhage was diagnosed on the basis of bronchoscopy and CT examination in patients with rapidly progressive respiratory insufficiency or newly emerged hemoptysis. Artificial ventilation was started in majority of cases.Therapeutically were used high doses of steroids i.v. (1000 mg 3–5 times in the iv infusion), Cyclophosphamide pulse, and plasmapheresis in some cases. Results The group of patients consisted of 32 cases; the average age of patients was 54 years (20–71) years. In half of patients was the episode of DAH the first manifestation of the disease. 16 patients were pro3 ANCA-positive, 7 patients MPO-ANCA positive, 6 patient had known systemic connective tissue disease 46.8% of patients survive 3 years from the acute episode of DAH, including two with repeated hemorrhage. 15 patients died during the acute phase of the disease, 3 more died during next 3 years, two of them on an opportunistic infection. Steroids were used for all patients, cyclophosphamide in 71, plasmapheresis in 56%, and i.v. immunoglobulins for 6.25 percent of patients. Patients who survive 3 years after the acute episode, had significantly lower necessity of artificial ventilation (40 vs. 93%) against the fatal cases, unfavorable prognostic sign was long term connective tissue disease. Residual lung impairment is present in 53% of the surviving patients; the signs of pulmonary arterial hypertension are present in 20% of the surviving group. Conclusions Diffuse alveolar hemorrhage is a sudden life-threatening event with a high mortality rate (46%) in the acute phase and during the first 3 years after the acute episode (20% of survivors). Up to half of patients the episode of DAH may be the first manifestation of the disease. Survival of patient depends on rapid diagnosis and the initiation of intensive immunosuppressive therapy. Respiratory failure is the major negative quoad vitam prognostic factor. Suspect the diffuse alveolar bleeding is necessary always in the case of a rapidly progressive respiratory failure. Acute bronchoscopy and x-ray examination give diagnosis of DAH, which further specify the acute examination of ANCA antibodies (71% of the report was ANCA antibodies positive. Disclosure of Interest None declared

THU0315 Increasing Proportion of Concomitant Fibromyalgia in Rheumatoid Arthritis Cohort Corresponds to Growing Arthritis Activity Assessed by Composite Indices

Background Fibromyalgia (FM) is well described as a concomitant syndrome that can frequently accompany connective tissue diseases, especially rheumatoid arthritis (RA). In this epoch of modern biologic therapy and RA tight control effort it is essential to count various factors that can impact RA activity or modulate activity assessment. Objectives To compare proportional representation of FM in RA patients cohort according to increasing arthritis activity assessed by composite indices in a regional, monocentric, cross-sectional study. Methods Examination of 120 consecutive patients (pts) with RA was performed in the terciary outpatient rheumatology department. Diagnosis of concomitant FM was established according to ACR criteria (1990). Standard Manual Tender Point Survey was used for the examination of FM tender points. The following data were recorded: demographic data, tender point count (TPC), Fibromyalgia Impact Questionnarie (FIQ) score and RA activity composite indices (DAS-28, CDAI, SDAI). Short Form 36 items (SF-36) and Health Assessment Questionnaire (HAQ) were used for evaluation of quality of life (QOL) and functional disability, respectively. Statistical analysis was based on Students t-test or Fisher exact test (statistical significance level 0.05). Results Concomitant FM was diagnosed in 25 (20.8%) pts with RA, 4 men and 21 women. Comparing RA without FM (RAF-) and with FM (RAF+), there were no significant differencies in sociodemographic characteristics, laboratory inflammatory markers, RF and ACPA seropositivity. RAF+ pts in comparison to RAF- pts reached significantly higher scores of RA activity (DAS-28 5.35±1.1 vs. 3.67±1.4, p<0.0001) and disability level (HAQ 1.83±0.64 vs. 0.87±0.76, p<0.0001). Analysing RA subgroups on the basis of rising disease activity we found increasing proportion of RAF+ pts in the subgroup with higher activity (DAS-28 <3.1 – 2.7% RAF+ pts; DAS-28 3.2-5.1 – 13.5%; DAS-28 >5.1 – 54.8%, p<0.0001). Similar results were found using other composite indices CDAI and SDAI. Conclusions Concomitant fibromyalgia appears frequently in RA pts and has significant impact on the disease activity assessment and disability level because of altered pain perception. Patients with high disease activity measured by widely used composite indices are usually indicated for more intensive immunosuppressive or biologic therapy. But in this case it is necessary to realize this group contains higher portion of FM pts resulting in risk of wrong therapy reinforcement. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5942

AB0591 Acute Respiratory Failure - the Reason for Urgent Rheumatologic Examination?

Background Acute respiratory failure is a reason for urgent admission to ICU. Statistical data show, that about 10 percent of deaths of respiratory failure patients on ICU is caused by diffuse alveolar hemorrhage syndrome (DAH). Barring infection, coagulation defects or oncological therapy complications, systemic connective tissue diseases must be considered as a reason. Less frequently there are patients with known systemic disease, more frequently DAH is the first manifestation of connective tissue disease, especially systemic vasculitis or SLE. Methods During 8 years 24 cases of diffuse alveolar hemorrhage in rheumatologic diseases were treated, 22 on ICU. 21 of them needed artificial ventilation. We observed the symptoms of preceded systemic disease, autoantibodies in time of DAH, hospital mortality and follow up of patients. Results 13 women and 11 men were affected, average age was 52,6 (21-74) years. Only in 32% of them had known diagnosis of systemic connective tissue disease before episode of alveolar hemorrhage. Diagnose of DAH was assessed by bronchoscopy with examination of bronchoalveolar lavage fluid and X-ray or CT results. 21 patients needed artificial ventilation.Most frequent immunological feature was ANCA antibody in 75% of our group. Proteinase -3 specificity was present in 58%, myeloperoxidase in 16% of our patients. ANA antibodies were founded in 21% of our patients, in one patient there was atypical anti GBM antibodies.Antiphospholipid antibodies were not present. Negative results had 20,8% of our group. Patients were treated by pulse methylprednisolone therapy, plasmapheresis, and i.v. Cyclophosphamide or i.v. immunoglobulins in cases where immunosuppressive therapy was contraindicated. Hospital mortality was 42 percent (10 patients). 14 patients are followed on outpatient base, in 3 of them chronic hemodialysis for irreversible renal failure is necessary, Early diagnosis and start of intensive immunomodulating therapy were one of crucial factors for survival of this life-threatening complication, however intensive immunosuppression is high-risky in patients with artificial ventilation support. Conclusions Diffuse alveolar hemorrhage is one of the important reasons of acute respiratory failure. In significant part of such patients the systemic connective tissue disease, mostly systemic vasculitis, is the cause of complication. Serious episode of DAH may be the first manifestation of rheumatologic disease. Bronchoscopic examination for DAH may be performed as early as possible, therefore early start of immunosuppressive therapy is crucial for survival of such patients. Outside of bronchoscopy instant assessment of ANCA antibodies is helpful. References West S, Arulkumaran N, Ind PW, Pusey CD Diffuse alveolar haemorrhage in ANCA-associated vasculitis. Intern Med. 2013;52(1):5-13. Acknowledgements Supported by MH CZ - DRO (UHHK, 00179906) Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4884

FRI0329 Free light chains of immunoglobulins in serum as biomarkers of activity in systemic lupus erythematosus

Background The molecules of immunoglobulins (Ig) include two identical heavy and two identical light chains. More light than heavy chains of Ig are produced under physiological conditions, and so free light chains (FLC) may be detected in biological fluids, especially in serum. Systemic lupus eryhtematosus (SLE) is associated with polyclonal activation of B cells, and proportional elevation of FLC kappa and FLC lambda values in serum should be expected in active form of SLE. Objectives To explore the changes of serum concentration of FLC kappa and FLC lambda as putative biomarkers of SLE disease activity in a prospective, comparative, and cross-over study. Methods Eighty-three adult SLE pts (ACR/1982, updated 1997) and 33 age- and sex-matched healthy controls were enrolled; concomitant infection, monoclonal gammopathy and renal failure in SLE pts were excluded. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K): a score ≥ 6 was considered clinically important. FLC kappa and FLC lambda in serum were analysed by quantitative nephelometric assay (Freelite, The Binding Site Group, Birmingham, UK) and compared against SLEDAI-2K score and serological biomarkers IgG, C3, C4 (Beckman Coulter), “total” ANA/IF (DIA SORIN, USA) in maximal titre, anti-dsDNA/IFCL (INOVA, USA) in maximal titre, and antinucleosome Abs/ELISA (EUROIMMUN, BRD). The data obtained were statistically processed using Medcalc-Statistical Software progamme. Results Serum concentration of FLC kappa, FLC lambda and total FLC kappa+FLC lambda in 22 SLE with SLEDAI-2K ≥ 6, and also in 61 SLE with SLEDAI-2K < 6 was significantly higher against healthy controls (p=0.003- < 0.001) except FLC lambda in SLE with SLEDAI-2K < 6 (p > 0.05). In SLE with SLEDAI-2K ≥ 6 the concentration of FLC kappa, FLC lambda and FLC kappa+FLC lambda was always significantly higher than in SLE with SLEDAI-2K < 6 (p < 0.001). In total group of 83 SLE was found significant correlation (p < 0.001) between SLEDAI-2K score and FLC kappa (r = 0.56), FLC lambda (r = 0.58), and FLC kappa+FLC lambda (r = 0.62); FLC analysis against serological biomarkers under study demonstrated a strong correlation namely between antinucleosome Abs and FLC kappa (r = 0.59), FLC lambda (r = 0.53) and FLC kappa+FLC lambda (r = 0.59). Conclusions The data obtained are suggesting that investigation of FLC values in serum should be useful as biomarkers of SLE disease activity, but further studies are necessary. Disclosure of Interest: Z. Hrncir Grant/research support from: PRVOUK P37-08, M. Drahosova Grant/research support from: PRVOUK P37-08, T. Soukup: None Declared, J. Toms: None Declared

THU0344 DAS-28, SDAI and CDAI in the patients with rheumatoid arthritis and concomitant fibromyalgia

Background Composite indices DAS-28 (Disease Activity Score, assessing 28 joints), SDAI (Simplified Disease Activity Index), CDAI (Clinical Disease Activity Index) are widely used instruments for the assessment of disease activity in the patients (pts) with rheumatoid arthritis (RA), but they may not be sufficient to evaluate activity in cases of RA associated with chronic pain syndromes such as fibromyalgia (FM). Objectives To examine the FM impact on disease activity composite indices in pts with RA. Methods We examined 120 pts (29 males, 91 females) with RA on the presence of concomitant FM according the ACR criteria (1990). All the patients were examined by the same rheumatologist, assessing TJC (tender joint count), SJC (swollen joint count) and TPC (tender point count). Laboratory parameters included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). RA activity was evaluated by three composite indices (DAS-28, SDAI and CDAI) and functional disability by Health Assessment Questionnaire (HAQ). Results The diagnosis of FM was established in 25 (20.8%) pts with RA (RAF), 4 men and 21 women. RA and RAF pts did not differ significantly in sociodemographic characteristics (age, eduacation, marital status, RA duration), laboratory inflammatory markes, RF and ACPA seropositivity. RAF pts in comparison to RA pts were found to reach significantly higher scores in all three composite indices (DA-28 5.35±1.1 vs. 3.67±1.4, p<0.0001; SDAI 31.8±10.9 vs. 13.5±10.8, p<0.0001; CDAI 29.6±10.7 vs. 11.8±9.4, p<0.0001) and in disability level (HAQ 1.83±0.64 vs. 0.87±0.76, p<0.0001). Detailed analysis revealed that TJC and VAS-GH (patient’s global health on a 100 mm visual analog scale) contributed mostly to the disease activity diferencies in RA and RAF, but doctor’s global health VAS was also significantly increased in pts with RAF in comparison to RA. Conclusions Rheumatologists, using disease activity composite indices in a daily clinical practice and clinical trials, should be aware of the limitations when these indices do not reflect real inflammatory activity but result from measurements dependent on an individual patient’s pain perception. Disclosure of Interest None Declared